Imidazole → HCID 67182450, compound

HRID 1807949Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:16])([O:10][CH2:11][C@@H:12]([OH:15])[CH2:13][OH:14])[CH3:9])=[CH:4][CH:3]=1.N1C=CN=C1.[C:22]([Si:26](Cl)([CH3:28])[CH3:27])([CH3:25])([CH3:24])[CH3:23].O>O1CCCC1.CN(C)C1C=CN=CC=1>[C:22]([Si:26]([CH3:28])([CH3:27])[O:14][CH2:13][C@H:12]([OH:15])[CH2:11][O:10][C:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)([CH3:16])[CH3:9])([CH3:25])([CH3:24])[CH3:23]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (S)-3-[1-(4-fluoro-phenyl)-1-methyl-ethoxy]-propane-1,2-diol (0.46 g) in tetrahydrofuran (6 ml) were added imidazole (0.32 g) and 4-dimethylaminopyridine (catalytic amount). The mixture was cooled to 0° C. and a solution of tert-butyl(chloro)dimethylsilane (0.32 g) in tetrahydrofuran (2 ml) was added dropwise. After 2 hours at 0° C., the reaction mixture was allowed to stir at room temperature for 16 hours. Water was added and the mixture was extracted twice with diethylether. The combined organic layers were dried (MgSO4) and evaporated. The crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc 90:10->75:25) to give (R)-1-(tert-butyl-dimethyl-silanyloxy)-3-[1-(4-fluorophenyl)-1-methyl-ethoxy]-propan-2-ol (0.57 g, 83%) as a colorless liquid. 1H NMR (300 MHz, CDCl3, δ): 0.00 (s, 6H), 0.82 (s, 9H), 1.48 (s, 6H), 2.49 (bs, 1H), 3.15 (d, J=4 Hz, 2H), 3.56 (t, J=4 Hz, 2H), 3.68 (m, 1H)

Workup

extractionthe mixture was extracted twice with diethylether
dry with materialThe combined organic layers were dried (MgSO4)
customevaporated
customThe crude product was purified by column chromatography (SiO2; gradient: heptane/EtOAc 90:10->75:25)

Sources & evidence

ORD record: ord-b8314d2828ae4af88589c7e76d1988cf
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08357712B2

Reaction notes

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